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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrathecal administration of prostaglandin E(2) (PGE(2)) produces mechanical hyperalgesia, thermal hyperalgesia, and touch-evoked allodynia in rats. Experiments were conducted to examine the effects of intrathecal administration of relatively selective PGE(2) receptor (EP receptor) agonists to establish which spinal EP receptors mediate these behavioral effects of spinally administered PGE(2). Administration of either sulprostone (EP(3) receptor agonist) or PGE(1) alcohol (EP(4) receptor agonist) produced marked mechanical and thermal hyperalgesia and touch-evoked allodynia. Neither 17-phenyl trinor PGE(2) (EP(1) receptor agonist) nor butaprost (EP(2) receptor agonist) produced any significant changes in behavioral response thresholds to mechanical or thermal stimuli. However, 17-phenyl trinor PGE(2) (EP(1) receptor agonist) did produce marked touch-evoked allodynia. These data suggest that in rats activation of spinal EP(3) and EP(4) receptors by PGE(2) is important for development of both mechanical and thermal hyperalgesia as well as for touch-evoked allodynia. PGE(2)-induced allodynia also appears to involve activation of spinal EP(1) receptors.
J Pain 2003 Sep
PMID:Spinal EP receptors mediating prostaglandin E2-induced mechanical hyperalgesia, thermal hyperalgesia, and touch-evoked allodynia in rats. 1462 81

Harpagophytum procumbens (Pedaliaceae) has been used for the treatment of pain and arthritis. The effect of Harpagophytum procumbens against lipopolysaccharide-induced inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, reverse transcription-polymerase chain reaction, prostaglandin E(2) (PGE(2)) immunoassay, and nitric oxide detection on mouse fibroblast cell line L929. The aqueous extract of Harpagophytum procumbens was shown to suppress PGE(2) synthesis and nitric oxide production by inhibiting lipopolysaccharide-stimulated enhancement of the cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) mRNAs expressions in L929 cells. These results suggest that Harpagophytum procumbens exerts anti-inflammatory and analgesic effects probably by suppressing cyclooxygenase-2 and iNOS expressions.
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PMID:Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. 1464 56

This study was designed to test the hypotheses that pain syndromes associated with specific body regions reflect unique properties of sensory neurons innervating these regions and/or unique responses of these afferents to tissue damage. Acutely dissociated adult rat dorsal root ganglia (DRG) neurons retrogradely labeled from either the colon or the glabrous skin of the hindpaw were studied by whole cell patch-clamp recording in current-clamp mode. Two populations of colonic afferent neurons were studied: pelvic afferents (arising from L(6), S(1), and S(2) DRG = LS DRG) and hypogastric/lumbar colonic afferents (arising from T(13), L(1), and L(2) DRG = TL DRG). Passive and active electrophysiological properties were studied before and after application prostaglandin E(2) (PGE(2)). We observed marked differences between cutaneous and colonic sensory neurons with respect to baseline passive and active electrophysiological properties as well as both the magnitude and pattern of PGE(2)-induced changes in excitability, passive, and active properties. There were also significant differences between TL and LS neurons with respect to baseline and PGE(2)-induced changes in several passive and active electrophysiological properties. Our results suggest that differences between cutaneous and colonic neurons reflect differences in pattern and/or density of ionic currents present in the plasma membrane. More interestingly, the ionic currents underlying the PGE(2)-induced sensitization of cutaneous neurons appeared to differ from those underlying the sensitization of colonic neurons. The implication of this observation is that it may be possible, in fact necessary, to treat pain arising from specific body regions with unique therapeutic interventions.
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PMID:Cutaneous and colonic rat DRG neurons differ with respect to both baseline and PGE2-induced changes in passive and active electrophysiological properties. 1473 64

A group of chemical mediators, the eicosanoids, is critical players in a multitude of physiological processes. Generated by the action of the cyclooxygenase (COX) enzyme on arachidonic acid they are responsible for diverse and often opposing actions such as platelet function, vasomotor tone, gastric cytoprotection and inflammation. Since their discovery several decades ago, our knowledge concerning their synthesis, function as natural ligands and methods to manipulate their activity through drug development has expanded. Traditional Non Steroidal Anti-Inflammatory Drugs (NSAIDs) are nonselective inhibitors of the COX enzyme, of which two isoforms are known to exist - COX-1 and COX-2. NSAIDs have been the mainstay of treatment in the management of pain and inflammation associated with acute and chronic inflammatory conditions that affect more than 10 million Americans. Their efficacy in this regard is not questioned. However, gastrointestinal toxicity arising from chronic NSAID ingestion is common and limits their use in clinical practice. Gastrointestinal toxicity has been attributed to the blockade of the COX-1 mediated generation of the cytoprotective prostanoids, such as PGE(2) and PGI(2). Selective COX-2 inhibitors were designed to inhibit the production of COX-2 dependent inflammatory prostanoids and to leave intact the cytoprotective COX-1 products. The first of a new class of these selective COX-2 inhibitors - the coxibs- were introduced to the market in 1999. These compounds, while exhibiting similar efficacy to traditional NSAIDs, were associated with a reduced incidence of surrogate or actual indices of GI toxicity. Questions have been raised concerning the cardiovascular and renal profiles of these agents based on data from both small and large clinical studies. More recently, our increasing understanding of the relative contributions of both isoforms of the COX enzyme to individual components of vascular homeostais has allowed us to appreciate the cardiovascular and renovascular implications of selective COX-2 inhibition.
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PMID:Cardiovascular and renovascular implications of COX-2 inhibition. 1496 23

The purpose of this study was to examine the effects of 2 different anti-inflammatory drugs on gingival crevicular fluid (GCF) volume and on prostaglandin E(2) (PGE(2)) levels of the GCF during orthodontic tooth movement. A total of 36 extraction patients, aged 17.6 +/- 2.5 years (mean +/- standard deviation), were divided into 3 groups. Acetylsalicylic acid (aspirin) and rofecoxib (Vioxx, Merck, Whitehouse Station, NJ) were used for pain control in the first and second groups; the third group was used as a control. Gingival crevicular fluid was sampled at the beginning of tooth movement and at 24, 48, and 168 hours. An automated enzyme immunoassay was used to measure PGE(2) in GCF. The intragroup differences were evaluated with the Wilcoxon test, and the differences between the groups were determined with the Mann-Whitney U test. Gingival crevicular fluid volumes of the groups did not change significantly during the experimental period. Depending on the variations of fibroblast activation, PGE(2) levels of all the groups increased at 24 and 48 hours and decreased at 168 hours. When the drugs were compared, it was found that the inhibition effect of aspirin on PGE(2) was more than that of rofecoxib. The results suggest that rofecoxib can be used during orthodontic treatment, but further study is recommended.
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PMID:Comparison of some effects of acetylsalicylic acid and rofecoxib during orthodontic tooth movement. 1501 7

To study the effectiveness for the treatment of intermittent claudication (IC) of three drugs with antiplatelet effects, cilostazol, beraprost sodium, and prostaglandin E(1) (PGE(1)), by using a systemic review of literature and a meta-analysis. A search was undertaken for studies reported between 1966-2002 in the MEDLINE database, and references in published articles and reviews were obtained. Data for maximum walking distance (MWD), pain-free walking distance (PFWD), and adverse clinical events were extracted from the articles that met the inclusion criteria. The pooled estimates of the weighted mean differences (WMD) of MWD and PFWD for cilostazol were 52.19 m [95% confidence interval (CI) 32.08, 72.31] and 39.75 m [95% CI 23.39, 56.10], and those for PGE(1) were 100.27 m [95% CI 15.76, 184.78] and 55.73 [95% CI 21.54, 89.92], respectively. These differences were statistically significant between the test drugs and placebo. However there was no statistical significance difference between beraprost sodium and placebo, even though there was one study that showed a tendency for improvement in walking distance. The total rate of adverse clinical events in cilostazol and beraprost sodium was higher than that for placebo, while there was no statistical significant difference between PGE(1) and placebo, although PGE(1) had a higher tendency for adverse clinical events. The literature evaluation results and the meta-analysis suggest that these two drugs (cilostazol and PGE(1)) can be considered to be effective drugs for the treatment of IC. Due to current availability of only a few clinical reports, further studies are needed to clarify the efficacy of beraprost sodium in the treatment of IC.
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PMID:Studies on the effectiveness and safety of cilostazol, beraprost sodium, prostaglandin E1 for the treatment of intermittent claudication. 1517 67

It is widely accepted that prostaglandin (PG) E2 is the principal pro-inflammatory prostanoid and plays an important role in inflammatory pain. However whether PGE2 is involved in neuropathic pain remains unknown. PGE2 is produced from arachidonic acid via PGH2 by at least three PGE synthases (PGES), cytosolic PGES (cPGES), and membrane-associated PGES (mPGES)-1 and -2. In the present study, to clarify the involvement of PGE2 and identify PGES mediating neuropathic pain, we applied a neuropathic pain model prepared by L5 spinal nerve transection to mPGES-1 knockout (mPGES-1-/-) mice. Whereas they retained normal nociceptive responses, mPGES-1-/- mice did not exhibit mechanical allodynia and thermal hyperalgesia over a week. These results demonstrate that PGE2 produced by mPGES-1 is involved in neuropathic pain.
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PMID:Membrane-associated prostaglandin E synthase-1 is required for neuropathic pain. 1519 60

Recent years have seen significant advances in our understanding of the peripheral and spinal mechanisms through which prostaglandins contribute to nociceptive sensitization. By contrast, the possibility of a supraspinal contribution of these compounds to facilitated pain states has received relatively little attention. One possible mechanism through which prostaglandins could act supraspinally to facilitate nociception would be by recruitment of descending facilitation from brainstem pain-modulating systems. The rostral ventromedial medulla (RVM) is now known to contribute to enhanced responding in a variety of inflammatory and nerve injury models. Its major supraspinal input, the midbrain periaqueductal gray (PAG), expresses prostanoid receptors and synthetic enzymes. The aim of the present study was to determine whether direct application of prostaglandin E(2) (PGE(2)) within the ventrolateral PAG is sufficient to produce hyperalgesia, and whether any hyperalgesia could be mediated by recruiting nociceptive modulating neurons in the RVM. We determined the effects of focal application of PGE(2) in the PAG on paw withdrawal latency and activity of identified nociceptive modulating neurons in the RVM of lightly anesthetized rats. Microinjection of PGE(2) (50 fg in 200 nl) into the PAG produced a significant decrease in paw withdrawal latency. The PGE(2) microinjection activated on-cells, RVM neurons thought to facilitate nociception, and suppressed the firing of off-cells, RVM neurons believed to have an inhibitory effect on nociception. These data demonstrate a prostaglandin-sensitive descending facilitation from the PAG, and suggest that this is mediated by on- and off-cells in the RVM.
Pain 2004 Jul
PMID:Prostaglandin E2 in the midbrain periaqueductal gray produces hyperalgesia and activates pain-modulating circuitry in the rostral ventromedial medulla. 1527 94

Inflammation caused by tissue damage results in pain, reflecting an increase in excitability of the primary afferent neurons innervating the area. There is some evidence to suggest that altered function of voltage-gated sodium channels is responsible for the hyperexcitability produced by inflammatory agents, possibly acting through G-proteins, but the role of different channel subtypes has not been fully explored. The tetrodotoxin-resistant (TTX-R) sodium channel Na(v)1.9 is expressed selectively in C- and A-fibre nociceptive-type units and is upregulated by G-protein activation. In this study, we examined the effects of the inflammatory agent prostaglandin-E(2) (PGE(2)) on Na(v)1.9 current in both Na(v)1.8-null and wild-type (WT) mice and explored the role of specific G-proteins in modulation. PGE(2) caused a twofold increase in Na(v)1.9 current (p<0.05) in both systems. Steady-state activation was shifted in a hyperpolarizing direction by 6-8 mV and availability of channels by 12 mV. No differences in the activation and inactivation kinetics could be detected. The increase in current was blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of G(i/o) but not G(s) subunits. Our data indicate that Na(v)1.9 current can be increased during inflammation via a G-protein dependent mechanism and suggest that this could contribute to the regulation of electrogenesis in dorsal root ganglia (DRG) neurons.
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PMID:PGE2 increases the tetrodotoxin-resistant Nav1.9 sodium current in mouse DRG neurons via G-proteins. 1537 52

The antihyperalgesic effect of pentoxifylline was investigated in three experimental pain models. Pentoxifylline (0.5-1.6 mg kg(-1)) given 30 min before the stimulus significantly inhibited the writhing response induced by the intraperitoneal (i.p.) administration of either acetic acid (-90%) or zymosan (-83%), but not that of iloprost, in mice, as well as the zymosan-induced articular hyperalgesia in the zymosan arthritis in rats (-50%). Pentoxifylline also inhibited the mechanical hypernociception in rats induced by the intraplantar injection of either carrageenin (-81%), bradykinin (-56%) or tumor necrosis factor alpha (TNF-alpha; -46%), but not that induced by interleukin-1beta (IL-1beta) or prostaglandin E(2) (PGE(2)). Pentoxifylline did not inhibit the nociceptive response in the hot plate test in mice. Further, the antinociceptive effect of pentoxifylline in the writhing test in mice and the zymosan-induced articular hyperalgesia were not reversed by the coadministration of the opioid receptor antagonist naloxone. Thus, pentoxifylline antinociceptive effect is probably not mediated at a central level. Pentoxifylline significantly reduced TNF-alpha (-43%) and IL-1beta (-42%) concentrations in the joint exudates of rats stimulated by intra-articular injection of zymosan and the production of both cytokines (-66 and -86%, respectively) by mouse peritoneal macrophages stimulated in vivo with zymosan as well as the expression of TNF-alpha at the tissue level in carrageenin-injected rat paws. In conclusion, the antinociceptive activity of pentoxifylline is associated with the inhibition of the release of both TNF-alpha and IL-1beta.
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PMID:Antihyperalgesic effect of pentoxifylline on experimental inflammatory pain. 1552 47


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